The gonadotropins, follicle stimulating hormone (FSH), luteinizing hormone (LH), and chorionic gonaotropin (CG) are required for ovulation, spermatogenesis, and the biosynthesis of sex steroids. A single hypothalamic hormone, gonadotropin-releasing hormone (GnRH, also known as luteinizing hormone-releasing hormone, LHRH, Sequence ID. No. 1) is responsible for regulating the secretion of both FSH and LH in mammals.
In recent years considerable research effort has been expended on finding synthetic analogs of LHRH. These efforts have produced a number of LHRH agonists and antagonists. One such LHRH agonist is leuprolide (Sequence ID. No. 2), a nonapeptide having the structure: ##STR1## which is disclosed and claimed in U.S. Pat. No. 4,005,063 to Gendrich, et al. Leuprolide is a potent LHRH agonist which, when introduced to the portal circulation, induces the release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the anterior pituitary. The oral bioavailability of leuprolide is low, hence the drug is typically administered either subcutaneously in daily doses as the acetate salt or monthly by intramuscular injection of a prolonged-release depot formulation in which the acetate salt is encapsulated in microcapsule form.
Various non-parenteral routes of administration of leuprolide acetate have been tested with limited success including aerosol formulations, nasal spray formulations, and iontophoretic systems.